title: CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype.
abstract: BACKGROUND
  CHARGE syndrome is a highly variable, multiple congenital anomaly syndrome, of which the complete phenotypic spectrum was only revealed after identification of the causative gene in 2004. CHARGE is an acronym for ocular coloboma, congenital heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear anomalies associated with deafness. This typical combination of clinical features is caused by autosomal dominant mutations in the CHD7 gene.
  
  
  OBJECTIVE
  To explore the emerging phenotypic spectrum of CHD7 mutations, with a special focus on the mild end of the spectrum.
  
  
  METHODS
  We evaluated the clinical characteristics in our own cohort of 280 CHD7 positive patients and in previously reported patients with CHD7 mutations and compared these with previously reported patients with CHARGE syndrome but an unknown CHD7 status. We then further explored the mild end of the phenotypic spectrum of CHD7 mutations.
  
  
  RESULTS
  We discuss that CHARGE syndrome is primarily a clinical diagnosis. In addition, we propose guidelines for CHD7 analysis and indicate when evaluation of the semicircular canals is helpful in the diagnostic process. Finally, we give updated recommendations for clinical surveillance of patients with a CHD7 mutation, based on our exploration of the phenotypic spectrum and on our experience in a multidisciplinary outpatient clinic for CHARGE syndrome.
  
  
  CONCLUSIONS
  CHARGE syndrome is an extremely variable clinical syndrome. CHD7 analysis can be helpful in the diagnostic process, but the phenotype cannot be predicted from the genotype.
authors.affiliation: Department of Genetics, University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: J E H
authors.initials: JE
authors.lastname: Bergman
authors.forename: N
authors.initials: N
authors.lastname: Janssen
authors.forename: L H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: M C J
authors.initials: MC
authors.lastname: Jongmans
authors.forename: R M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: C M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
mesh_terms: D058747:CHARGE Syndrome / Q000175:diagnosis* / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human